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Lactate AND Metformin

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https://www.readbyqxmd.com/read/29762537/the-cardioprotective-effect-of-metformin-in-doxorubicin-induced-cardiotoxicity-the-role-of-autophagy
#1
Rita Zilinyi, Attila Czompa, Andras Czegledi, Andrea Gajtko, Dora Pituk, Istvan Lekli, Arpad Tosaki
The molecular mechanisms underlying doxorubicin-induced cardiotoxicity are still being investigated, but are known to involve oxidative stress, mitochondrial dysfunction, and the dysregulation of autophagy. The objective of the current study was to examine the protective role of metformin and its effect on autophagy in doxorubicin-induced cardiotoxicity. Sprague⁻Dawley rats were divided into four groups at random. The doxorubicin-treated group received doxorubicin (3 mg/kg every second day) intraperitoneally...
May 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29761830/itc-commentary-on-metformin-clinical-drug-drug-interaction-study-design-that-enables-an-efficacy-and-safety-based-dose-adjustment-decision
#2
Maciej J Zamek-Gliszczynski, Xiaoyan Chu, Jack A Cook, Joseph M Custodio, Aleksandra Galetin, Kathleen M Giacomini, Caroline A Lee, Mary F Paine, Adrian S Ray, Joseph A Ware, Matthias B Wittwer, Lei Zhang
Metformin drug-drug interaction (DDI) studies are conducted during development of drugs that inhibit organic cation transporters and/or multidrug and toxin extrusion proteins (OCTs/MATEs). Monitoring solely changes in systemic exposure, the typical DDI study endpoint appears inadequate for metformin, which is metabolically stable, has poor passive membrane permeability, and undergoes transporter-mediated tissue distribution and clearance. Evaluation of renal clearance, antihyperglycemic effects, and potentially lactate as an exploratory safety marker, can support rational metformin dose adjustment...
May 15, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29738843/transporter-dependent-cytotoxicity-of-antiviral-drugs-in-primary-cultures-of-human-proximal-tubular-cells
#3
Lawrence H Lash, Caroline A Lee, Clynn Wilker, Vishal Shah
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively...
May 5, 2018: Toxicology
https://www.readbyqxmd.com/read/29738540/risk-of-lactic-acidosis-in-type-2-diabetes-patients-using-metformin-a-case-control-study
#4
Abdellatif Aharaz, Anton Pottegård, Daniel Pilsgaard Henriksen, Jesper Hallas, Henning Beck-Nielsen, Annmarie Touborg Lassen
BACKGROUND: Metformin constitutes first-line treatment of type 2 diabetes mellitus. It is presumed to have lactic acidosis as a dangerous, but rare, side effect. OBJECTIVES: To estimate the incidence rate of lactic acidosis in patients with type 2 diabetes mellitus as well as to estimate the relative risk of lactic acidosis associated with metformin treatment. METHODS: This is a population-based combined cohort and case-control study among patients with type 2 diabetes mellitus who were acutely admitted with lactic acidosis at Odense University Hospital, Denmark; in the period from 1st June 2009 to 1st October 2013...
2018: PloS One
https://www.readbyqxmd.com/read/29710486/synergistic-and-non-synergistic-effects-of-salmon-calcitonin-and-omega-3-fatty-acids-on-antioxidant-anti-inflammatory-and-haematological-indices-in-diabetic-rats
#5
Wale Johnson Adeyemi, Luqman Aribidesi Olayaki
The optimum therapy for the management of diabetes mellitus (DM) has been a controversial issue. Therefore, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids {eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); EPA/DHA ratio?=?3/2} relative to metformin in diabetic male Wistar rats. Forty rats were used for this study. They were randomly divided into 8 groups of five (5) rats each, which were treated with single or combined administration of salmon calcitonin, N-3 and metformin...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29658305/liver-antioxidant-and-aerobic-status-improves-after-metformin-and-melatonin-administration-in-a-rat-model-of-high-fat-diet-and-mammary-carcinogenesis
#6
Natalia Kurhaluk, Bianka Bojková, Pawel J Winklewski
Oxidative stress is involved in the development of various cancers. In the present study the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive/curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive products (TBARS) as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP, aldehyde and ketone derivates)...
April 15, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29614026/prenatal-metformin-therapy-attenuates-hypertension-of-developmental-origin-in-male-adult-offspring-exposed-to-maternal-high-fructose-and-post-weaning-high-fat-diets
#7
You-Lin Tain, Kay L H Wu, Wei-Chia Lee, Steve Leu, Julie Y H Chan
Widespread consumption of a Western diet, comprised of highly refined carbohydrates and fat, may play a role in the epidemic of hypertension. Hypertension can take origin from early life. Metformin is the preferred treatment for type 2 diabetes. We examined whether prenatal metformin therapy can prevent maternal high-fructose plus post-weaning high-fat diets-induced hypertension of developmental origins via regulation of nutrient sensing signals, uric acid, oxidative stress, and the nitric oxide (NO) pathway...
April 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29609531/metformin-associated-lactic-acidosis-a-case-series-of-28-patients-treated-with-sustained-low-efficiency-dialysis-sled-and-long-term-follow-up
#8
Andrea Angioi, Gianfranca Cabiddu, Maura Conti, Gianfranco Pili, Alice Atzeni, Valeria Matta, Riccardo Cao, Matteo Floris, Marco Songini, Maria Franca Mulas, Mitchell Rosner, Antonello Pani
BACKGROUND: Metformin associated lactic acidosis (MALA) is a well-known serious side effect of biguanides. However, the best treatment strategy remains a matter of debate. In the last 14 years, we observed a significant increase in hospitalizations for MALA to our Center. We report the outcomes of our clinical and therapeutic approach. METHODS: This is a single-center case series. Twenty-eight patients affected with MALA and acute kidney failure admitted between January 2000 and September 2014 were included...
April 2, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29609037/%C3%AE-cyano-4-hydroxycinnamate-impairs-pancreatic-cancer-cells-by-stimulating-the-p38-signaling-pathway
#9
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29574345/range-of-therapeutic-metformin-concentrations-in-clinical-blood-samples-and-comparison-to-a-forensic-case-with-death-due-to-lactic-acidosis
#10
C Hess, M Unger, B Madea, B Stratmann, D Tschoepe
Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death...
March 12, 2018: Forensic Science International
https://www.readbyqxmd.com/read/29550639/effect-of-metformin-on-estrogen-and-progesterone-receptor-positive-mcf-7-and-triple-negative-mda-mb-231-breast-cancer-cells
#11
Inês Amaral, Cláudia Silva, Ana Correia-Branco, Fátima Martel
This work aimed to investigate the effect of metformin on cellular glucose uptake and metabolism by breast cancer cells, as a mechanism contributing to its anticancer properties. Estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines were used as in vitro models of breast cancer. Short-term (26 min) exposure of MCF-7 and MDA-MB-231 cells to metformin inhibited uptake of 3 H-deoxy-D-glucose (3 H-DG). In contrast, long-term (24 h) exposure to metformin (5 μM-1 mM) concentration-dependently increased 3 H-DG uptake in both cell lines...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29534338/-massive-metformin-overdose
#12
Angela L Chiew, Daniel F B Wright, Nicola M Dobos, Kylie McArdle, Ahmed A Mostafa, Annemarie Newth, Michael S Roberts, Geoffrey K Isbister
Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old woman presented 5 h after multidrug overdose, including 132 g extended-release metformin. Continuous venovenous haemodiafiltration (CVVHDF) and noradrenaline were commenced due to metabolic acidosis (pH 7.0, lactate 17 mmol l-1 ) and shock. Despite 3 h of CVVHDF, her acidosis worsened (pH 6.83, lactate 24 mmol l-1 ). Intermittent haemodialysis (IHD) improved acidosis (pH 7.13, lactate 26 mmol l-1 ) but again worsened (pH 6...
March 13, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29520235/lactate-induced-glucose-output-is-unchanged-by-metformin-at-a-therapeutic-concentration-a-mass-spectrometry-imaging-study-of-the-perfused-rat-liver
#13
Giulio Calza, Elisabeth Nyberg, Matias Mäkinen, Rabah Soliymani, Annunziata Cascone, Dan Lindholm, Emanuele Barborini, Marc Baumann, Maciej Lalowski, Ove Eriksson
Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29484415/metformin-facilitates-bg45%C3%A2-induced-apoptosis-via-an-anti%C3%A2-warburg-effect-in-cholangiocarcinoma-cells
#14
Dehua Tang, Lei Xu, Mingming Zhang, Robert Gregory Dorfman, Yida Pan, Qian Zhou, Lixing Zhou, Yuming Wang, Yang Li, Yuyao Yin, Lei Wang, Xiaoping Zou
Cholangiocarcinoma (CCA) is a highly lethal malignancy with an often late diagnosis and consequent poor prognosis. Chemotherapy is the only therapeutic strategy for most patients. Compared to normal cells, tumor cells preferentially metabolize glucose to lactate, even in aerobic conditions. Such metabolic alterations not only support the growth and invasion of tumor cells, but also promote their chemoresistance. The purpose of our study was to explore the role of metformin in regulating the metabolism of CCA, as well as to investigate whether metformin could act as a chemosensitizer of the HDAC3 inhibitor BG45, and therefore have potential for the treatment of CCA...
April 2018: Oncology Reports
https://www.readbyqxmd.com/read/29465046/clinical-and-laboratory-features-of-metformin-intoxication-in-suicidal-patients-attending-an-intensive-care-unit
#15
A Cetinkaya, D Avci, A Erden, O Akca, O Ozer, U Kalan, A I Gunal
Introduction: This study has been performed for the purpose of researching the complications occurred at patients who took metformin overdose in an attempt to suicide. None of the patients has the diagnosis of diabetes mellitus and never used metformin. Materials and Methods: This retrospective cross-sectional study was carried out with 21 patients who has neither diagnosed diabetes mellitus nor taken metformin for suicide before. Results: It was observed that there is a moderate, negative (r = -0...
February 2018: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/29457876/pharmacokinetics-of-metformin-in-patients-with-gastrointestinal-intolerance
#16
Laura J McCreight, Tore B Stage, Paul Connelly, Mike Lonergan, Flemming Nielsen, Cornelia Prehn, Jerzy Adamski, Kim Brøsen, Ewan R Pearson
AIMS: To assess potential causes of metformin intolerance, including altered metformin uptake from the intestine, increased anaerobic glucose utilization and subsequent lactate production, altered serotonin uptake, and altered bile acid pool. METHODS: For this pharmacokinetic study, we recruited 10 severely intolerant and 10 tolerant individuals, matched for age, sex and body mass index. A single 500-mg dose of metformin was administered, with blood sampling at 12 time points over 24 hours...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29456175/metformin-induced-lactic-acidosis-mila-review-of-current-diagnostic-paradigm
#17
Lauren Krowl, Hassan Al-Khalisy, Pratibha Kaul
A new diagnostic paradigm has been proposed to better categorize causes of Metformin-Associated Lactic Acidosis (MALA). The diagnostic criteria defines a link between Metformin and lactic acidosis if lactate is >5mmol/L, Ph<7.35 and Metformin assay >5mg/L. Metformin assays are not readily available in emergency departments including nationwide Veteran's Affairs Hospitals; thereby making this proposed classification tool difficult to use in today's clinical practice. We describe a case report of a 45-year-old male, who took twice the amount of Metformin prescribed and presented with Metformin-induced lactic acidosis...
May 2018: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29427160/metformin-associated-lactic-acidosis-a-case-report
#18
Takehide Umeda, Taro Minami, Keith Bartolomei, Eleanor Summerhill
A 54-year-old woman with type 2 diabetes mellitus, hypertension, and peripheral vascular disease developed life-threatening lactic acidosis during treatment with metformin for type 2 diabetes. The woman received metformin at 1000 mg orally twice a day for type 2 diabetes. She presented to our emergency department with a 3-day history of severe watery diarrhea, nausea, and vomiting. Her grandson whom she cared for had gastroenteritis several days prior to the onset of her symptoms. She was confused and hypotensive with a blood pressure of 70/39 mmHg...
February 9, 2018: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29386513/hexokinase-2-depletion-inhibits-glycolysis-and-induces-oxidative-phosphorylation-in-hepatocellular-carcinoma-and-sensitizes-to-metformin
#19
Dannielle DeWaal, Veronique Nogueira, Alexander R Terry, Krushna C Patra, Sang-Min Jeon, Grace Guzman, Jennifer Au, Christopher P Long, Maciek R Antoniewicz, Nissim Hay
Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained...
January 31, 2018: Nature Communications
https://www.readbyqxmd.com/read/29318219/extending-metformin-use-in-diabetic-kidney-disease-a-pharmacokinetic-study-in-stage-4-diabetic-nephropathy
#20
Ajith Munasinghe Dissanayake, Mark Christopher Wheldon, Jafar Ahmed, Christopher John Hood
Introduction: Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. Methods: In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy...
July 2017: KI Reports
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